ABSTRACT
An eight-step stereodivergent synthesis of enantiomerically pure (-)-14-epi-pseudotabersonine and (+)-pseudotabersonine has been developed from a common N-tert-butanesulfinyl ketimine key intermediate.
ABSTRACT
A new route to spiro-oxetanes, potential scaffolds for drug discovery, is described. The route is based on the selective 1,4-C-H insertion reactions of metallocarbenes, generated from simple carbonyl precursors in flow or batch mode, to give spiro-ß-lactones that are rapidly converted into spiro-oxetanes. The three-dimensional and lead-like properties of spiro-oxetanes are illustrated by the conversion of the 1-oxa-7-azaspiro[3,5]nonane scaffold into a range of functionalized derivatives.
Subject(s)
Drug Design , Ethers, Cyclic/chemistry , Spiro Compounds/chemistry , Carbon/chemistry , Crystallography, X-Ray , Hydrazones/chemistry , Hydrogen/chemistry , Lactones/chemical synthesis , Lactones/chemistry , Molecular Conformation , Oxidation-ReductionABSTRACT
A highly selective N-sulfinylimidate aldolization has been developed under mildly basic conditions leading to diastereopure products of high synthetic potential. The innate reversibility of this aldolization was suppressed by the use of titanium as the Lewis acid. An application of this methodology via the synthesis of a potential neurotransmitter reuptake inhibitor is illustrated.
ABSTRACT
Treating readily available α-diazo-ß-ketoesters with HBF(4) results in nucleophilic fluorination by the usually inert and stable tetrafluoroborate anion. The resulting α-fluoro-ß-ketoesters are highly versatile synthetic intermediates, for example in the preparation of fluoro-heterocycles, as illustrated by the direct formation of fluoro-pyrimidines, -pyrazoles and -coumarins in a single step.
Subject(s)
Boric Acids/chemistry , Borates , Coumarins/chemistry , Esters , Halogenation , Pyrazoles/chemistry , Pyrimidines/chemistryABSTRACT
We have developed an in-flow process for the synthesis of ß-keto esters via the BF(3)·OEt(2)-catalyzed formal C-H insertion of ethyl diazoacetate into aldehydes. The ß-keto esters were then condensed with a range of amidines to give a variety of 2,6-substituted pyrimidin-4-ols.
